This application will examine structural and functional aspects of HIV-1 integration. The specific aims include: A. Analyzing the integrase active site by site-directed mutagenesis. B. Establishing methods for purifying and concentrating HIV-1 preintegration complexes. C. Examination of higher order protein-protein and protein-DNA interactions important for preintegration complex activity. D. Develop an assay for authentic integration of exogenous HIV-1 DNA.